Phosphoinositide 3-Kinase-C2α Regulates Polycystin-2 Ciliary Entry and Protects against Kidney Cyst Formation

摘要: Signaling from the primary cilium regulates kidney tubule development and cyst formation. However, mechanism controlling targeting of ciliary components necessary for morphogenesis signaling is largely unknown. Here, we studied function class II phosphoinositide 3-kinase-C2α (PI3K-C2α) in renal tubule-derived inner medullary collecting duct 3 cells show that PI3K-C2α resides at recycling endosome compartment proximity to base. In this subcellular location, controlled activation Rab8, a key mediator cargo protein cilium. Consistently, partial reduction was sufficient impair elongation transport polycystin-2, as well alter proliferation signals linked polycystin activity. agreement, heterozygous deletion mice induced defects tubules predisposed animals development, either genetic models polycystin-1/2 or response ischemia/reperfusion-induced damage. These results indicate required such loss enzyme exacerbate pathogenesis cystic disease.